Contralateral prophylactic mastectomy in a rural population: A single-institution experience.

Background: The incidence of contralateral prophylactic mastectomy (CPM) for unilateral breast cancer (UBC) has continued to increase, despite an absent survival benefit except in populations at highest risk for developing contralateral breast cancer (CBC). CPM rates may be higher in rural populations but causes remain unclear. A study performed at our institution previously found that 21.8 % of patients with UBC underwent CPM from 2000 to 2009. This study aimed to evaluate the CPM trend at a single institution serving a rural population and identify the CPM rate in average-risk patients. Methods: Retrospective review of patients who underwent mastectomies for UBC at our institution from 2017 to 2021 was performed. Analysis utilized frequencies and percentages, descriptive statistics, chi-square, and independent sample t-tests. Results: A total of 438 patients were included, of whom 64.4 % underwent bilateral mastectomy for UBC (CPM). Patients who underwent CPM were significantly younger, underwent genetic testing, had germline pathogenic variants, had a family history of breast cancer, had smaller tumors, underwent reconstruction, and had more wound infections. Of CPM patients, 50.4 % had no identifiable factors for increased risk of developing CBC. Conclusions: The rate of CPM in a rural population at a single institution increased from 21.8 % to 64.4 % over two decades, with an average-risk CPM rate of 50.4 %. Those that undergo CPM are more likely to undergo reconstruction and have more wound infections. Identifying characteristics of patients undergoing CPM in a rural population and the increased associated risks allows for a better understanding of this trend to guide conversations with patients. Key message: This study demonstrates that the rate of contralateral prophylactic mastectomy for unilateral breast cancers performed at a single institution serving a largely rural population has nearly tripled over the last two decades, with half of these patients having no factors that increase the risk for developing contralateral breast cancers. Contralateral prophylactic mastectomy was significantly associated with smaller tumors, younger age, genetic testing, germline pathogenic variants, family history of breast cancer, breast reconstruction, and increased wound infections.

The Development of Breast Cancer-Related Lymphedema After Mastectomy in a Rural Population.

Breast cancer-related lymphedema (BCRL) is a lifelong condition that can impact the quality of life, affecting approximately 20% of breast cancer patients. Risk factors for the development of BCRL after mastectomy in rural populations have not been studied.Retrospective review of mastectomy patients from 2017 to 2021 was performed at a single institution. Statistical analysis included logistic and linear regression models.475 patients were included, and 40 (8.4%) patients were diagnosed with BCRL. Increased odds of developing BCRL were significantly associated with tumor-involved lymph nodes, radiation therapy, axillary lymphadenectomy, adjuvant chemotherapy, and endocrine therapy. Postmastectomy reconstruction significantly reduced the odds of developing BCRL. There was no significant association in our population with age, body mass index, diabetes, tobacco use, cancer type, or complications.This study demonstrates that individuals underrepresented in the literature, such as patients in largely rural communities, have some differences in risk factors for developing BCRL when compared to national studies.

Adenosquamous carcinoma of the breast, an uncommon diagnosis with poor prognosis-Lessons learned from a 12-year analysis of the National Cancer Database.

We compared the clinicopathologic characteristics and prognosis of adenosquamous carcinoma (ASQ) of the breast with invasive ductal carcinoma (IDC), utilizing the National Cancer Database (NCDB) from 2004 to 2015. 1 932 688 female patients had invasive breast carcinoma; 1 421 250 had IDC (73.5%); and 453 had ASQ (0.0002%). When compared to IDC, ASQ patients were significantly (P < .05) older and had grade 1 tumors; negative lymph nodes; ER/PR/HER2-negative tumors; and worse 5-year overall survival (64.9% vs 74%, respectively). Our study, largest to date on ASQ, revealed an aggressive carcinoma with a significantly worse prognosis than IDC. "Personalized medicine" treatment approach for patients with this uncommon carcinoma is needed.

Nomogram update based on TAILORx clinical trial results - Oncotype DX breast cancer recurrence score can be predicted using clinicopathologic data.

OBJECTIVES: Oncotype DX (ODX), 21-gene breast cancer (BC) assay, predicts risk of recurrence and benefits of addition of chemotherapy to hormonal therapy for early-stage BC. We previously published a nomogram/calculator that could predict ODX results without performing the test by using clinicopathologic characteristics of BC available from pathology reports. Patients with intermediate-risk (11-25) ODXRS (RS) were excluded from that nomogram. This update tests the predictive value of clinicopathologic variables for forecasting the ODXRS while including intermediate-risk-ODXRS patients and stratifying ODXRS based on recently published TAILORx clinical trial results (0-25 = low-risk, 26-100 = high-risk-ODXRS; intermediate-risk-ODXRS belongs to the low-risk category). MATERIAL AND METHODS: The nomogram was built on 65,754 ODX-tested ER+/HER2-/lymph-node-negative patients with 6-50 mm tumor, captured by the National Cancer Data Base (NCDB) from 2010 to 2014. Five clinicopathologic variables (age, tumor size, grade, progesterone-receptor status (PR) and BC-histologic type) were assessed with logistic regression to predict for a low-risk (0-25) or a high-risk (26-100) ODXRS. Results were validated on a separate 18,585 ODX-tested cohort from 2015. RESULTS: Grade and PR were the highest significant predictors of both low-risk and high-risk-ODXRS, followed by histologic type, tumor size and age. The Receiver Operator Characteristic (ROC) curve showed strong statistical model for both low-risk and high-risk-ODXRS prediction outcomes (c-index = 0.81). CONCLUSIONS: An updated nomogram is now developed/validated on the entire population of ODX-tested patients (84,339) captured by the NCDB. The nomogram/calculator, available on-line at the UTMCK/Shiny website (https://utgsm.shinyapps.io/OncotypeDXCalculator/), will continue serving as a surrogate for BC patients for which ODX testing is not affordable, available or necessary.

Oncotype DX breast cancer recurrence score can be predicted with a novel nomogram using clinicopathologic data.

PURPOSE: Oncotype DX (ODX) recurrence score (RS) breast cancer (BC) assay is costly, and performed in only ~1/3 of estrogen receptor (ER)-positive BC patients in the USA. We have now developed a user-friendly nomogram surrogate prediction model for ODX based on a large dataset from the National Cancer Data Base (NCDB) to assist in selecting patients for which further ODX testing may not be necessary and as a surrogate for patients for which ODX testing is not affordable or available. METHODS: Six clinicopathologic variables of 27,719 ODX-tested ER+/HER2-/lymph node-negative patients with 6-50 mm tumor size captured by the NCDB from 2010 to 2012 were assessed with logistic regression to predict high-risk or low-risk ODXRS test results with TAILORx-trial and commercial cut-off values; 12,763 ODX-tested patients in 2013 were used for external validation. The predictive accuracy of the regression model was yielded using a Receiver Operator Characteristic analysis. Model fit was analyzed by plotting the predicted probabilities against the actual probabilities. A user-friendly calculator version of nomograms is available online at the University of Tennessee Medical Center website (Knoxville, TN). RESULTS: Grade and progesterone receptor status were the highest predictors of both low-risk and high-risk ODXRS, followed by age, tumor size, histologic tumor type and lymph-vascular invasion (C-indexes-.0.85 vs. 0.88 for TAILORx-trial vs. commercial cut-off values, respectively). CONCLUSION: This is the first study of this scale showing confidently that clinicopathologic variables can be used for prediction of low-risk or high-risk ODXRS using our nomogram models. These novel nomograms will be useful tools to help physicians and patients decide whether further ODX testing is necessary and are excellent surrogates for patients for which ODX testing is not affordable or available.

Evolving Trends and Influencing Factors in Mastectomy Decisions.

It is known that survival is unaffected by the choice of surgical management for breast cancer (BC) patients. Despite this fact, recent literature reveals that the number of bilateral mastectomies (BMs) in the United States is increasing. In an effort to elucidate potential factors influencing this trend, we investigated socioeconomic and clinicopathologic characteristics of our patient cohort that could have affected a patient's decision between unilateral mastectomy (UM) versus BM. Five-hundred-eight patients with unilateral BC who underwent mastectomy between 2000 and 2009 were analyzed: 397-UM; 111-BM. Influence of patient's age, insurance status, residence (rural versus urban), subsequent reconstruction, marital status, smoking history, family cancer history, cancer stage and grade on the BM versus UM patient's decision were analyzed using independent sample t tests, χ2 and logistic regression analysis. BM was more likely to be chosen by younger (<50 years) patients (P < 0.001); patients with private insurance [odds ratio (OR) = 2.22, 95% confidence interval (CI) = 1.4-3.5]; residence in urban settings (OR = 5.09, 95% CI = 2.5-10.4); and plans for subsequent reconstruction (OR = 2.31, 95% CI = 1.4-3.8). Marital status, smoking history, family cancer history, BC stage and grade did not significantly impact patient's choice of BM versus UM. We found that patients with unilateral BC who are younger (<50 year) have private insurance, reside in urban settings, or plan for subsequent reconstruction are more likely to undergo BM for unilateral BC. Genetic specific data were not evaluated for this patient cohort, and will be the subject of future analysis.

Utilization and impact of 21-gene recurrence score assay for breast cancer in clinical practice across the United States: lessons learned from the 2010 to 2012 National Cancer Data Base analysis.

The aim of our study is to investigate patient selection for the 21-gene recurrence score assay (RS) for breast cancer (BC) and the RS impact on chemotherapy administration (Chemo) in clinical practice across the United States through the retrospective observational study of National Cancer Data Base (NCDB) patients from 2010 to 2012. NCDB captures ~70 % of all newly diagnosed malignancies in the USA annually. The 2010-2012 period depicts data from the beginning of the NCDB that required recording of molecular assays and their data release in April 2015. De-identified demographic and clinical variables of patients that had RS results were analyzed. 513,080 patients had BC; 406,525 were estrogen receptor-positive (ER+). 74,334/91,651 patients with RS recorded as a numerical value (0-100) were analyzed (18.2 % of ER+). Patients' ages ranged from 18 to 90 (mean = 58.8, median = 59); 99.1 % were females. Patients of Caucasian race, from regions with <7 % having no high school education, and >$63,000 median household income were more likely to be tested than patients of other races, education, or income (p < 0.001). 58.1 % of tests were performed in ER+/lymph node-negative/>1 cm tumors; 16.4 % included ≥N1 disease; 9.9 % included T1a, T3, Stage III and IV, or HER2-positive cancers. Low-risk RS result had 92.2 % negative predictive value for no Chemo. Intermediate-risk RS result had 40.1 % positive predictive value (PPV); high-risk RS had 81.2 % PPV for Chemo. RS is obtained in ~1/5 of ER + BC patients across the USA. Further studies investigating influence and implementation of the newest evidence-based management guidelines regarding patients' selection for RS test and chemotherapy administration upon obtaining of test results are warranted.

Pretreatment depression severity in breast cancer patients and its relation to treatment response to behavior therapy.

OBJECTIVE: Major depressive disorder is prevalent in breast cancer patients. There is a paucity of research on variables associated with depression severity and the link between depression severity and response to psychotherapy. To provide optimal mental health services to breast cancer patients, examining correlates of depression severity and its relation to treatment response is critical. METHOD: In the context of a randomized trial of behavior activation and problem-solving therapy for depressed breast cancer patients, this study evaluated demographic (marital status, age, education), psychosocial (social support, environmental reward, anxiety, number of coexistent anxiety disorders), and cancer-related (bodily pain, length of diagnosis, cancer stage) variables associated with pretreatment depression severity. Second, the relation of pretreatment depression severity with posttreatment and 12-month response and remission was assessed. RESULTS: For pretreatment depression severity, the overall regression model accounted for 40% of the variance, F(5, 74) = 9.87, p < .001. Less environmental reward and greater somatic anxiety were significantly and uniquely associated with depression severity. Depression severity was unrelated to treatment remission but was a significant moderator of treatment response at posttreatment and 12-month follow-up; individuals with higher depression severity were more responsive to therapy. For patients treated with behavior activation, environmental reward significantly mediated the relationship between pre- and posttreatment depression. CONCLUSIONS: Consistent with behavioral models of depression, less environmental reward and greater anxiety might influence depression severity in breast cancer patients. Data support the efficacy of behavior therapy for breast cancer patients, particularly those with more severe depression.

Behavior therapy for depressed breast cancer patients: predictors of treatment outcome.

OBJECTIVE: Major depressive disorder (MDD) is the most common psychiatric disorder among breast cancer patients and is associated with substantial functional impairment. Although several outcome studies have explored the utility of psychotherapy for breast cancer patients with subsyndromal depression symptoms, only a few clinical trials have explored the efficacy of behavior therapy for patients with well-diagnosed MDD. An additional limitation of this research is that little is known about factors that best predict treatment outcome. METHOD: In the context of a recent randomized trial of behavior activation and problem-solving therapy for depressed breast cancer patients (n = 80; Hopko et al., 2011), this study explored predictors of treatment outcome with selected demographic (age, education, marital status, occupational status), psychosocial (pretreatment depression and environmental reward, coexistent anxiety disorders, social support, history of psychotherapy) and cancer-related variables (cancer stage, duration of cancer diagnosis, and cancer treatment). RESULTS: Positive treatment outcome as defined by Beck Depression Inventory-II (Beck et al., 1996) response and remission criteria was associated with being married, increased social support, not actively undergoing cancer treatment during psychotherapy, and having a history of psychotherapy. CONCLUSIONS: The efficacy of behavior therapy for depressed breast cancer patients may depend on several patient variables. Implications for the provision of behavior therapy for breast cancer patients are discussed.

Odontogenic ameloblast-associated protein (ODAM) inhibits growth and migration of human melanoma cells and elicits PTEN elevation and inactivation of PI3K/AKT signaling.

BACKGROUND: The Odontogenic Ameloblast-associated Protein (ODAM) is expressed in a wide range of normal epithelial, and neoplastic tissues, and we have posited that ODAM serves as a novel prognostic biomarker for breast cancer and melanoma. Transfection of ODAM into breast cancer cells yields suppression of cellular growth, motility, and in vivo tumorigenicity. Herein we have extended these studies to the effects of ODAM on cultured melanoma cell lines. METHODS: The A375 and C8161 melanoma cell lines were stably transfected with ODAM and assayed for properties associated with tumorigenicity including cell growth, motility, and extracellular matrix adhesion. In addition, ODAM-transfected cells were assayed for signal transduction via AKT which promotes cell proliferation and survival in many neoplasms. RESULTS: ODAM expression in A375 and C8161 cells strongly inhibited cell growth and motility in vitro, increased cell adhesion to extracellular matrix, and yielded significant cytoskeletal/morphologic rearrangement. Furthermore, AKT activity was downregulated by ODAM expression while an increase was noted in expression of the PTEN (phosphatase and tensin homolog on chromosome 10) tumor suppressor gene, an antagonist of AKT activation. Increased PTEN in ODAM-expressing cells was associated with increases in PTEN mRNA levels and de novo protein synthesis. Silencing of PTEN expression yielded recovery of AKT activity in ODAM-expressing melanoma cells. Similar PTEN elevation and inhibition of AKT by ODAM was observed in MDA-MB-231 breast cancer cells while ODAM expression had no effect in PTEN-deficient BT-549 breast cancer cells. CONCLUSIONS: The apparent anti-neoplastic effects of ODAM in cultured melanoma and breast cancer cells are associated with increased PTEN expression, and suppression of AKT activity. This association should serve to clarify the clinical import of ODAM expression and any role it may serve as an indicator of tumor behavior.

Primary cutaneous melanoma arising in a long-standing irradiated keloid.

Ionizing radiation has been used therapeutically for a variety of clinical conditions, including treatment of hypertrophic keloids. Keloids may rarely be associated with malignancy, but the use of low-dose ionizing radiation is associated with an increased risk of cutaneous malignancies. We describe a case in which a primary desmoplastic melanoma arose in a long-standing, previously irradiated keloid.

The effect of multiple wire localization in breast conservation.

Variability exists regarding the surgical technique in breast conservation therapy. The purpose of this project was to determine differences between single (SH) or flanking (FH) hooked needle localization wires used for nonpalpable breast lesions. We retrospectively reviewed 201 female patients at a single institution from 2004 to 2008. All patients had biopsy-proven ductal carcinoma in situ or invasive disease. Comparisons were made in regard to margin status, reoperation, completion mastectomy, size of lesion, and breast specimen volume. SH was placed in 122 patients (61%) and FH in 79 patients (39%). In SH, 23 patients (18%) had positive margins and 31 patients (25%) had reoperations as compared with 31 patients (25%) with positive margin and 36 patients (44%) in the FH cohort (P = 0.039 and 0.0037). Average lesion size and volume resected was 1.5 cm and 137 cm(3) in SH and 2.85 cm and 188 cm(3) in FH, respectively (P = 0.0001 and 0.006). Positive margins were associated with lesion size and not volume of tissue excised. The FH technique was associated with more positive margins, reoperation, and completion mastectomy.

Brief behavioral activation and problem-solving therapy for depressed breast cancer patients: randomized trial.

OBJECTIVE: Major depression is the most common psychiatric disorder among breast cancer patients and is associated with substantial impairment. Although some research has explored the utility of psychotherapy with breast cancer patients, only 2 small trials have investigated the potential benefits of behavior therapy among patients with well-diagnosed depression. METHOD: In a primarily Caucasian, well-educated sample of women (age = 55.4 years, SD = 11.9) diagnosed with breast cancer and major depression (n = 80), this study was a randomized clinical trial testing the efficacy of 8 sessions of behavioral activation treatment for depression (BATD) compared to problem-solving therapy. Primary outcome measures assessed depression, environmental reward, anxiety, quality of life, social support, and medical outcomes. RESULTS: Across both treatments, results revealed strong treatment integrity, excellent patient satisfaction with treatment protocols, and low patient attrition (19%). Intent-to-treat analyses suggested both treatments were efficacious, with both evidencing significant pre-post treatment gains across all outcome measures. Across both treatments, gains were associated with strong effect sizes, and based on response and remission criteria, a reliable change index, and numbers-needed-to-treat analyses, approximately ¾ of patients exhibited clinically significant improvement. No significant group differences were found at posttreatment. Treatment gains were maintained at 12-month follow-up, with some support for stronger maintenance of gains in the BATD group. CONCLUSIONS: BATD and problem-solving interventions represent practical interventions that may improve psychological outcomes and quality of life among depressed breast cancer patients. Study limitations and future research directions are discussed.

Clinical integration of picture archiving and communication systems with pathology and hospital information system in oncology.

The complexity of our current healthcare delivery system has become an impediment to communication among caregivers resulting in fragmentation of patient care. To address these issues, many hospitals are implementing processes to facilitate clinical integration in an effort to improve patient care and safety. Clinical informatics, including image storage in a Picture Archiving and Communication System (PACS), represents a tool whereby clinical integration can be accomplished. In this study, we obtained intraoperative photographs of 19 cases to document clinical stage, extent of disease, disease recurrence, reconstruction/grafting, intraoperative findings not identified by preoperative imaging, and site verification as part of the Universal Protocol. Photographs from all cases were stored and viewed in PACS. Images from many of the cases were presented at our interdepartmental cancer conferences. The stored images improved communication among caregivers and preserved pertinent intraoperative findings in the patients' electronic medical record. In the future, pathology, gastroenterology, pulmonology, dermatology, and cardiology are just a few other subspecialties which could accomplish image storage in PACS. Multidisciplinary image storage in a PACS epitomizes the concept of clinical integration and its goal of improving patient care.

Odontogenic ameloblast associated protein as a novel biomarker for human breast cancer.

Odontogenic Ameloblast Associated Protein (ODAM) is a protein isolated in ameloblasts during odontogenesis. ODAM expression was identified in breast cancer, but its significance remains unknown. The purpose of this study is to determine if ODAM expression can serve as a prognostic marker and provide information regarding treatment in human breast cancer. Breast cancer patients were identified from our tumor registry from 1993 to 2003. Archived breast cancer tissue from 243 patients (stage 0 = 53, stage I = 51, stage II = 53, stage III = 47, stage IV = 39) was stained using monoclonal antibody for ODAM. Presence or absence of immunostaining was correlated with stage, histologic grade, response to chemotherapy, and survival using chi2 and logistic regression analyses. Tumor nuclear staining for ODAM increased with increasing group stage (P < 0.001). Staining for ODAM did not correlate with histologic grade or chemotherapy (P = 0.558, P = 0.093). Improved outcomes within each stage were noted with ODAM staining, statistically significant for stages 0, I, and II (P < 0.001, P = 0.003, P = 0.003) and underpowered for stages III and IV (P = 0.724, P = 0.059). Survival benefit associated with tumor nuclear staining increased with advancing stage (P < 0.001). These results show that ODAM predicts survival in breast cancer. Research is ongoing to determine ODAM's clinical utility and role in carcinogenesis.

Cognitive-behavior therapy for depressed cancer patients in a medical care setting.

Major depression is the most common psychiatric disorder among cancer patients and is associated with decreased quality of life, significant deterioration in recreational and physical activities, relationship difficulties, sleep problems, more rapidly progressing cancer symptoms, and more metastasis and pain relative to nondepressed cancer patients. Although some research has explored the utility of psychological interventions with cancer patients, only one study to date has explored the potential benefits of cognitive-behavior therapy among cancer patients with well-diagnosed depression. Addressing this gap in the literature, this study represents an open clinical trial to assess the effectiveness of a brief Cognitive-Behavioral Treatment for Depression (CBTD) among depressed cancer patients in a medical care setting. Results revealed strong treatment integrity, good patient compliance, excellent patient satisfaction with the CBTD protocol, and significant pre-post treatment gains across a breadth of outcome measures assessing depression, anxiety, quality of life, and medical outcomes. These gains also were associated with strong effect sizes and generally maintained at 3-month follow-up. Behavioral activation interventions, especially when paired with cognitive techniques, may represent a practical medical care treatment that may improve psychological outcomes and quality of life among cancer patients. Study limitations and future research directions are discussed.

The phenomenology and screening of clinical depression in cancer patients.

Clinical depression is the most common psychiatric disorder among cancer patients and is associated with significant functional impairment. Unfortunately, depression in cancer patients is often under- diagnosed and untreated, and studies examining the predictive utility of assessment instruments in detecting clinically depressed cancer patients are sparse. Using a structured interview, thirty-three patients with various cancer types were diagnosed as having major depression (n = 24) or no psychiatric diagnosis (n = 9). All patients were administered the Beck Depression Inventory-II (BDI-II), the Center for Epidemiological Studies in Depression Scale (CES-D), Hamilton Rating Scale for Depression (HRSD), Quality of Life Inventory (QOLI), a medical and psychosocial functioning questionnaire (SF-36), and given co-morbidity of depression with anxiety disorders, the Beck Anxiety Inventory (BAI). Depressed and non-depressed cancer patients were compared and contrasted across all assessment measures and accuracy of instruments was based on evaluating their sensitivity, specificity, and positive predictive values. Depressed cancer patients exhibited more severe depressive symptoms and poorer quality of life, increased anxiety and bodily pain, and decreased vitality and social functioning. All instruments exhibited strong predictive properties, with the CES-D and BDI-II considered most feasible given their time efficiency, administrative simplicity, and strong psychometric properties.

Breast health education for working women in Appalachia: insights from focus group research.

BACKGROUND: This study seeks to understand rural working women, their knowledge of health systems, and how breast health issues fit into their lives. A key aim of this study was to identify regionally and culturally specific factors that influence how these women approach breast health and to identify ways that more positive breast health behaviors can be achieved. METHODS: Five focus groups (N = 42) were conducted among women at sites where the Breast Health Outreach Program (BHOP) had been conducted. Focus groups were composed of 7 to 10 women who were in about the same age cohort. RESULTS: Women provided multiple insights about their attitudes and behaviors related to breast heath concerns. Analysis of the data revealed that many of the comments clustered around two types of "systems" in these women's lives: the professional health care system and personal community systems. The BHOP provides a bridge between these two systems and seems to facilitate positive actions. Workplace health professionals also provide a bridge between professional and personal systems. CONCLUSIONS: Women exhibited the general distrust of the medical system that the literature indicates is often associated with Appalachian culture. However, this study found that distrust can be overcome with education programs that meet women where they live and work. Such programs are most likely to be successful when the materials and methods are sensitive to Appalachian culture and when medical services are brought into the community.